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J Pharm Pharmacol. 2013 Apr;65(4):512-20. doi: 10.1111/jphp.12013. Epub 2012 Dec 14.

Synthesis and in-vitro antimicrobial evaluation of a high-affinity iron chelator in combination with chloramphenicol.

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1
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.

Abstract

OBJECTIVES:

The objectives of this study were first to design and synthesize a hexadentate chelator with high iron(III) affinity and, second, to evaluate its antimicrobial activity in the presence and absence of chloramphenicol.

METHODS:

A hexadentate ligand was synthesized by conjugating a protected bidentate compound onto a tripodal structure. The pKa values and iron affinity of the chelator were determined by spectophotometric titration. Minimum inhibitory concentrations were determined by visual inspection of broth turbidity. The bactericidal rates were calculated by counting the colony numbers on a light board after incubation with and without an antimicrobial agent.

KEY FINDINGS:

A hexadentate 3-hydroxypyridin-4-one was found to possess a high affinity for iron(III), with a pFe value of 31.2 (negative logarithm of concentration of the free iron(III) in solution (when [Fe³⁺](Total)  = 10⁻⁶) M; [Ligand](Total)  = 10⁵ M; pH = 7.4). We found that this chelator had an appreciable inhibitory effect in vitro against the two bacterial strains Providencia stuartii and Staphylococcus aureus, particularly in the presence of chloramphenicol.

CONCLUSIONS:

A 3-hydroxypyridin-4-one hexadentate ligand has potential as an antimicrobial agent. Combination therapy with this iron chelator plus chloramphenicol has potential for the treatment of extracellular infections.

PMID:
23488779
DOI:
10.1111/jphp.12013
[Indexed for MEDLINE]
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